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Healthed

There’s no way you’d want to go to work when you’ve got the telltale signs of gastro: nausea, abdominal cramps, vomiting and diarrhoea. But what about when you’re feeling a bit better? When is it safe to be around colleagues, or send your kids to school or daycare? The health department recommends staying home from work or school for a minimum of 24 hours after you last vomited or had diarrhoea. But the question of how long someone is contagious after recovering from gastro is a very different question.   What causes gastro? To better understand how long you can be contagious with gastro, we need to look at the various causes. Viruses are the most common causes of gastro. Rotavirus is the leading cause in infants and young children, whereas norovirus is the leading cause of gastro in adults. There are around 1.8 million cases of norovirus infection in Australia each year. This accounts for almost 40% of the total cases of gastro. Bacterial gastroenteritis is also common and accounts for around 1.6 million cases a year. Of those cases, 1.1 million come from E. coli infections. Other bacteria that commonly cause gastro include salmonella, shigella and campylobacter. These bacteria are often found in raw or undercooked meat, seafood, and unpasteurised milk. Parasites such as giardia lamblia, entamoeba histolytica and cryptosporidium account for around 700,000 cases of gastro per year. Most of the time people recover from parasitic gastroenteritis without incident, but it can cause problems for people with weaker immune systems. Read more: Health Check: I feel a bit sick, should I stay home or go to work?   Identifying the bug Most cases of diarrhoea are mild, and resolve themselves with no need for medical attention. But some warrant further investigation, particularly among returned travellers, people who have had diarrhoea for four or five days (or more than one day with a fever), patients with bloody stools, those who have recently used antibiotics, and patients whose immune systems are compromised. The most common test is the stool culture which is used to identify microbes grown from loose or unformed stools. The bacterial yield of stool cultures is generally low. But if it does come back with a positive result, it can be potentially important for the patient. Some organisms that are isolated in stool cultures are notifiable to public health authorities. This is because of their potential to cause serious harm in vulnerable groups such as the elderly, young children, pregnant women and those with weakened immune systems. The health department must be notified of gastro cases caused by campylobacter, cryptosporidium, listeria, salmonella, shigella and certain types of E.coli infection. This can help pinpoint outbreaks when they arise and allow for appropriate control measures.   You might feel better but your poo isn’t Gastro bugs are spread via the the faecal-oral route, which means faeces needs to come into contact with the mouth for transmission to occur. Sometimes this can happen if contaminated faecal material gets into drinking water, or during food preparation. But more commonly, tiny particles of poo might remain on the hands after going to the toilet. Using toilet paper to wipe when you go to the toilet doesn’t completely prevent the contamination of hands, and even more so when the person has diarrhoea. The particles then make their way to another person’s mouth during food preparation or touching a variety of contaminated surfaces and then putting your fingers in your mouth. After completely recovering from the symptoms of gastro, infectious organisms can still be shed into stools. Faecal shedding of campylobacter, the E. coli O157 strain, salmonella, shigella, cryptosporidium, entamoeba, and giardia can last for many days to weeks. In fact, some people who have recovered from salmonella have shed the bacteria into their stools 102 days later. Parasites can remain alive in the bowel for a long period of time after diarrhoea finishes. Infectious cryptosporidium oocysts can be shed into stools for up to 50 days. Giardia oocysts can take even longer to be excreted.   So, how long should you stay away? Much of the current advice on when people can return to work, school or child care after gastro is based on the most common viral gastroenteritis, norovirus, even though few patients will discover the cause of their bug. For norovirus, the highest rate of viral shedding into stools occurs 24 to 48 hours after all symptoms have stopped. The viral shedding rate then starts to quickly decrease. So people can return to work 48 hours after symptoms have stopped. Yes, viral shedding into stools can occur for longer than 48 hours. But because norovirus infection is so common and recovery is rapid, it’s not considered practical to demand patients’ stools be clear of the virus before returning to work. While 24 hours may be appropriate for many people, a specific 48-hour exclusion rule is considered necessary for those in a higher-risk category for spreading gastro to others. These include food handlers, health care workers and children under the age of five at child care or play group. If you have a positive stool culture for a notifiable organism, that may change the situation. Food handlers, childcare workers and health-care workers affected by verotoxin E.coli, for example, are not permitted to work until symptoms have stopped and two consecutive faecal specimens taken at least 24 hours apart have tested negative for verotoxin E. coli. This may lead to a lengthy exclusion period from work, possibly several days.   How to stop the spread Diligently washing your hands often with soap and water is the most effective way to stop the spread of these gastro bugs to others. Consider this: when 10,000 giardia cysts were placed in the palm of a hand, handwashing with soap eliminated 99% of them. To prevent others from becoming sick, disinfect contaminated surfaces thoroughly immediately after someone vomits or has diarrhoea. While wearing disposable gloves, wash surfaces with hot water and a neutral detergent, then use household bleach containing 0.1% hypochlorite solution as a disinfectant.

Sullivan Nicolaides Pathology

Prenatal screening for chromosome disorders by maternal serum screening, ultrasound and non-invasive prenatal tests, such as Harmony®, is an established part of reproductive care in Australia. The overall risk of chromosome disorders rises markedly with maternal age, as shown in Figure 1. (There are two exceptions: Monosomy X, also known as Turner syndrome, and microdeletions, such as 22q11.2, occur independently of maternal age). This does not mean that chromosome screening should be restricted to older mothers. Younger mothers have more babies than older mothers, and the overall outcome is that the majority of pregnancies with a serious chromosome disorder occur in mothers under 35 years of age. For this reason, screening for chromosome disorders in pregnancy should be offered to mothers of all ages. The great majority of these chromosome disorders are new abnormalities that have happened for the first time in this pregnancy. They are not inherited disorders, and genetic testing of the parents provides no information about the risk of such an abnormality. This provides another reason for offering screening for chromosome disorders to all mothers, irrespective of family history.  

The frequency of single-gene disorders at birth

Chromosome disorders are not the only type of genetic condition which can affect the developing foetus. Many serious childhood disorders are due to recessive mutations that have been inherited from parents, with the parents being unaffected by these mutations. A parent who is a carrier of a recessive mutation, that is, having one normal and one abnormal copy of a gene, will not be affected by the abnormal gene. Everyone is a carrier for one or more disorders; this is of no immediate consequence and there usually is no family history of the disorder. The situation changes if both parents are carriers of mutations in the same gene located on one of the autosomes (chromosomes 1-22). The chance of their child inheriting the abnormal gene from each parent, and so developing an autosomal recessive disorder, is 25%. The situation is a little different for a woman with a recessive mutation on an X-chromosome: each of her sons is at 50% risk of inheriting the abnormal gene and being affected, and half of her daughters will be carriers. Overall, the risk of a woman who is an X-linked carrier having an affected child is approximately 25%. There are hundreds of inherited autosomal and X-linked recessive disorders that present in infancy and early childhood. These disorders are individually rare but, together, they are more common than the chromosome disorders for which prenatal screening is widely available and accepted. Further, the risk of these recessive disorders does not vary with maternal age (Figure 1). For mothers under 35 years of age, the risk of having a child with a serious childhood-onset recessive disorder is greater than the risk of having a child with a chromosome disorder.  

Screening potential parents for recessive disorders

These disorders are inherited but there is usually no family history to provide a clue. Until recently, the only way of identifying a carrier of a rare recessive disorder was to diagnose the disorder in their affected child. This has now changed. It is possible to screen a couple for mutations in autosomal genes, and a woman for mutations in X-linked genes, to determine whether they are at 25% risk of having an affected child. This screening test is called ’reproductive carrier screening’. From both a technical and clinical perspective, the challenge lies in choosing which genes to analyse. A number of providers, including Sonic Genetics, offer reproductive carrier screening for mutations responsible for three common disorders: cystic fibrosis and spinal muscular atrophy (both autosomal recessive) and Fragile X syndrome (X-linked recessive). Approximately 6% of people are carriers of one or more of these conditions, and 0.6% (one in 160) couples are at 25% risk of having an affected child. Those couples who are identified as carriers can consider a variety of options, including IVF with a donor gamete, pre-implantation genetic diagnosis, prenatal diagnosis by CVS, or they may make an informed decision to accept the risk. RANZCOG recommends that couples be offered such screening. The cost of this three-gene panel is approximately $400* per person. There is no Medicare rebate for carrier screening; there are exceptions (and restrictions) for people with a documented family history of cystic fibrosis or Fragile X syndrome.  

Expanded reproductive screening

If we were to screen more genes, we would identify more carriers. Sonic Genetics offers a screen of over 300 genes (autosomal and X-linked) which cause serious recessive childhood disorders. We estimate that approximately 70% of Australians are carriers for one or more conditions included in this screen and 3% (one in 30) couples are at 25% risk of having an affected child. This amounts to five times more information than is provided by the three-gene panel. This screen, the Beacon Expanded Carrier Screen, currently costs $995* per person or $1,750* for couples tested together. It is tempting to think that ‘more genes tested = more information for a couple’. This is not the case because the information provided by a carrier screen is also determined by the carrier frequency, mode of inheritance and detection rate of the assay for each gene. Some currently available screens of more than 100 genes provide less information than the three-gene screen described earlier.  

Implementing reproductive screening

Before offering reproductive carrier screening to your patients, it is important to consider some of the nuances, particularly in relation to the Fragile X syndrome (some carriers will develop premature ovarian failure or a tremor/ataxia syndrome in later life) and when there is a family history of a recessive disorder (seek expert advice; do not rely on screening). It is also important to recognise that some couples will not want this carrier information – and others will demand it. Each person needs to be free to make their own decision about what information they wish to have. We provide information about the three-gene and Beacon screens for both requestors and patients on our website. Sonic Genetics also offers genetic counselling free-of-charge for couples who are identified by either of these reproductive carrier screens as being at high risk of having an affected child (see www.sonicgenetics.com.au/rcs/gc).  

Conclusion

It is accepted practice that every woman is offered screening for chromosome disorders in pregnancy, irrespective of age and family history. In a similar vein, every couple should be offered reproductive carrier screening for recessive disorders, irrespective of age and family history. For women under 35 years, the risk of their child having a recessive disorder is greater than the risk of a chromosome disorder. Offering reproductive carrier screening simply represents good medical practice.  

References

RANZCOG. Prenatal screening and diagnostic testing for fetal chromosomal and genetic conditions. 2018 Aug. 35 p. Available from: https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Prenatal-screening.pdf?ext=.pdf Archibald AD, Smith MJ, Burgess T, Scarff KL, Elliott J, Hunt CE, et al. Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests. Genet Med. 2018; 20(5): 513-523 Available from https://www.ncbi.nlm.nih.gov/pubmed/29261177 doi:10.1038/gim.2017.134. Sonic Genetics [Internet]. c2015. Reproductive Carrier Screening; 2018. Available from: www.sonicgenetics.com.au/rcs   General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
Dr Linda Calabresi

It wasn’t that long ago that vitamin D appeared to be the panacea for everything from preventing MS to reducing the risk of diabetes. But the one area where we thought the benefit of this vitamin was not up for debate was bone health. It has been proven - lack of vitamin D causes rickets. It has been proven that vitamin D is important in bone metabolism and turnover. And it has been proven the people with low bone density are more likely to experience fractures. Therefore add vitamin D and improve bones, right? Wrong! The latest meta-analysis of more than 80 randomised controlled trials shows that vitamin D supplementation does not prevent fractures or falls, and does not have any consistently clinically relevant effects on bone mineral density. This comes as a bit of a surprise, to say the least. According to the systematic review, vitamin D had no effect on total fractures, hip fractures, or falls among the 53,000 participants in the pooled analysis. And it didn’t matter if higher or lower doses of vitamin D were used, the New Zealand researchers reported in The Lancet. In looking for a reason for the lack of an effect from supplementation, previous explanations such as baseline 25OHD of trial participants being too high, or the supplement dose being too low, or the trial being done in the wrong population just don’t hold water. The sheer number and variety of trials included in this meta-analysis has meant all of these possible confounders have been accounted for. “The trials we included have a broad range of study designs and populations, but there are consistently neutral results for all endpoints, including the surrogate endpoint of bone mineral density,” they said. Consequently, the researchers said future trials were unlikely to alter these conclusions. “There is little justification to use Vitamin D supplements to maintain or improve musculoskeletal health,” they stated. And while they acknowledge the clear exception to this is in the case of the prevention or treatment of rickets and osteomalacia, in general clinical guidelines should not be recommending vitamin D supplementation for bone health. The conclusion appears quite emphatic and definitive, and it is supported in an accompanying commentary by a leading US endocrinologist. “The authors should be complimented on an important updated analysis on musculoskeletal health,” said Dr Chris Gallagher from Creighton University Medical Centre, Omaha in the US. But he suggests many Vitamin D supporters will still be flying the flag for supplementation, pointing to the multiple potential non-bony benefits. “Within three years, we might have that answer because there are approximately 100,000 participants currently enrolled in randomised, placebo-controlled trials of vitamin D supplementation,” he said. “I look forward to those studies giving us the last word on vitamin D.”  

References

Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018 Oct 4. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30265-1 [epub ahead of print] Gallagher JC. Vitamin D and bone density, fractures, and falls: the end of the story? Lancet Diabetes Endocrinol. 2018 Oct 4. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30269-9 [epub ahead of print]
Dr Linda Calabresi

The answer to both these questions is yes according to Dr Darren Pavey, gastroenterologist and senior lecturer at the University of NSW. Speaking at the Healthed General Practice Education seminar in Sydney recently, Dr Pavey said there was good international research suggesting that many cases of chronic pancreatitis were going undiagnosed and the condition was far more prevalent than previously recognised. Overseas studies including cohorts of randomly selected adult patients suggest a prevalence of between 6-12%, with the condition being more likely among patients with recent onset type 2 diabetes, excess alcohol intake, smokers and those over 40 years of age, he said. And in response to the question of whether it is important to diagnose this condition, Dr Pavey said chronic pancreatitis not only caused immediate symptoms usually including pain, diarrhoea and weight loss but commonly had longer-term consequences such as pancreatic exocrine insufficiency (where there is less than 10% pancreatic function) and an increased risk of diabetes, malnutrition and even pancreatic cancer. Certainly, an incentive to diagnose and treat earlier rather than later. Part of the challenge in recognising the condition is that the classic triad of symptoms, namely abdominal pain, diarrhoea and weight loss are common to a variety of medical conditions including IBD and IBS. What’s more, abdominal pain, which many doctors would have thought had to be present with pancreatitis does not always occur in chronic pancreatitis especially when it is idiopathic which is the more common variety of chronic pancreatitis. In fact, pain is only present in about half the cases of idiopathic chronic pancreatitis. Idiopathic pancreatitis constitute 55% of all cases, the other 45% being alcohol-related. Abdominal pain tends to be a more consistent feature of alcoholic chronic pancreatitis. So if you have a patient in the right age group (about 40 to 60 years), who has chronic diarrhoea, weight loss and maybe abdominal pain and you suspect they might have chronic pancreatitis what do you do? The most common screening test for chronic pancreatitis is now a faecal elastase-1 stool test, requiring a single formed stool sample, said Dr Pavey. The test has a high specificity and sensitivity (both over 90%) and is readily available to Australian GPs, although it does not attract a Medicare rebate and costs approximately $60. The test is positive if the concentration of faecal elastase is less than 200mcg/g. In terms of imaging, CT is usually the option of first choice with signs of calcification and atrophy being pathognomonic of significant chronic pancreatitis. Aside from the need to stop drinking and smoking, treatment revolves around replacement of the pancreatic enzymes, which is available as a capsule taken orally (Creon). The deficiency of these enzymes is the chief cause of the diarrhoea, malabsorption, and weight loss so replacing them not only alleviates the symptoms but will also help prevent some of significant sequelae associated with this ongoing condition. Interestingly, a study of patients newly diagnosed with pancreatic cancer, showed that 66% had pancreatic exocrine insufficiency at diagnosis, and after two months this prevalence grew to 93% Dr Pavey advises starting patients with known chronic pancreatitis on 25,000 lipase units (Creon) with every meal and 10,000 units with every snack, and recommends patients eat six smaller meals during the day rather than three larger meals. This replacement therapy would then be titrated up to 40,000 units with a meal and 25,000 units for a snack. For those whose need was greater, replacement could even be increased to 80,000 units per meal. There was no need to put patients on a reduced fat diet when they were on pancreatic enzyme replacement therapy however they often had a highly acidic upper gastrointestinal environment and required acid suppression treatment. In conclusion, Dr Pavey advises clinicians to have a high index of suspicion for this poorly-recognised but important condition. “[Doctors] should be aware of the problem of underdiagnosing this condition and have a low threshold for checking faecal elastase and assessing pancreatic insufficiency,” he said.

Loubaba Mamluk

While heavy drinking is clearly harmful to the unborn baby, often leading to miscarriage, premature birth and foetal alcohol syndrome, the possible effects of light drinking have been less clear. High quality data on this issue is lacking due to ethical and methodological issues. On the one hand, experiments (clinical trials) in this area are impossible to conduct. Clinical trials would include randomising a group of pregnant women to drinking alcohol, which is clearly unethical. On the other hand, in observational studies we can never be sure whether the results are due to alcohol or other factors, such as wealth or education.

‘One glass is OK, isn’t it?’

Women often ask about “safe” levels of drinking during pregnancy. The distinction between light drinking and abstinence is indeed the point of most tension and confusion for health professionals and pregnant women, and public health guidance varies worldwide. Our new review of the evidence, published in BMJ Open, shows that this specific question is not being researched thoroughly enough. As there can be no clinical trial research carried out on this topic, we systematically reviewed all the data from a wide range of high quality observational studies. These studies involved pregnant women, or women trying to conceive, who reported on their alcohol use before the baby was born. The researchers assessed the impact of light drinking, compared with no alcohol at all.   >> Read More Source: The Conversation
Dr Linda Calabresi

New NHMRC guidelines put age and family history up front and centre in determining who should be screened for bowel cancer with colonoscopy and who needs iFOBT. It has been known for some time that family history can influence the risk of developing bowel cancer, Australia’s second most common cause of cancer death. But it is also known that specific, identified genetic mutations causing conditions such as Lynch syndrome or familial adenomatous polyposis are rare, accounting for less than 5% of all bowel cancers diagnosed. At most, the researchers say, this only explains half of the reasons why family history is a risk factor for bowel cancer. “The remainder of the observed increases in familial risk could be due in part to mutations in yet to be discovered colorectal cancer susceptibility genes, polygenic factors such as single-nucleotide polymorphisms, or dietary and other lifestyle factors shared by family members,” the guideline authors said in the Medical Journal of Australia. Therefore, the researchers, led by Professor Mark Jenkins, director of the Centre for Epidemiology and Biostatistics, in the University of Melbourne’s School of Population and Global Health, analysed all the available cohort studies to determine the risk of developing colorectal cancer based on age and family history. They categorised cohorts into one of three levels of risk and this determined at what age screening would be worthwhile starting and which screening method was most appropriate. The screening guidelines exclude people with a known or suspected cancer-causing genetic syndrome, as these people require much more intensive screening and should be managed in a family cancer clinic. The majority of Australians (90%) fall into the lowest risk category, category 1, which puts their risk at age 40 of developing colorectal cancer in the next 10 years at about 0.25% (one in 400). As with most other cancers age is a risk factor, so it is unsurprising that at age 50 the risk of developing this cancer has risen to 0.9%. Screening for this category 1 group should be the two-yearly iFOBT test that is currently available via the National Bowel Screening program for adults between the ages of 50 and 74 years. Interestingly, people aged 75 and older still develop bowel cancer but there have been no studies to determine the cost-effectiveness or benefit vs risk analysis of screening in this age group which is why the program and the guideline recommendations stop at 74 years. One of the differences in these new guidelines, a revision from the previous ones published back in 2005, is that people with a first degree relative who has had or has a bowel cancer at age 55 or older are still considered at average risk (category 1). However, people with this history might consider starting the iFOBT screening at a younger age (45 years), the guideline authors suggest. Category 2 includes people with a moderately increased risk of developing colorectal cancer, 3-6 times higher than average. This will mean having a first degree relative diagnosed with a bowel cancer before the age of 55 or having two first degree relatives who developed bowel cancer at any age (or one first degree and two second degree relatives). Category 2 people are recommended to have iFOBT every two years for the decade between ages 40 and 50 and then switch to five yearly colonoscopies until the age of 75. Finally, the high risk, category 3 is for all those patients without a genetic syndrome whose family history is even stronger than those people in category 2. Their risk is between 7-10 times higher than average. This includes people with at least three first-degree relatives who have been diagnosed with colorectal cancer at any age or people who have multiple relatives with the cancer including at least one diagnosed before aged 55. These high-risk people need to start screening earlier, with the guidelines recommending iFOBT every two years starting at age 35 and continuing for 10 years and then having a colonoscopy every five years between the ages of 45 and 75. Of note is that the revised guidelines have deleted the reference in the previous guidelines to starting screening 10 years before the earliest age colorectal cancer was diagnosed in a first degree relative. “There have been no studies conducted to determine the utility of beginning screening 10 years before the earliest diagnosis in the family, which was a recommendation in the 2005 guidelines and, therefore, it is not included in these guidelines,” they said. The new guidelines aim not only to more strongly define risk based on the latest evidence, but also to determine the most appropriate screening method based on that risk, taking into consideration cost-effectiveness and rationalisation of available services, in particular, colonoscopies.   Reference Jenkins MA, Ouakrim DA, Boussioutas A, Hopper JL, Ee HC, Emery JD, et al. Revised Australian national guidelines for colorectal cancer screening: family history. Med J Aust. 2018 Oct 29. doi: 10.5694/mja18.00142. [epub ahead of print]

Dr Linda Calabresi

No one wants to miss ovarian cancer especially in its early stages when you have a chance of successful treatment. But should we be regularly monitoring women who have had a simple ovarian cyst detected on ultrasound, as most guidelines recommend to avoid missing this particularly deadly cancer? That is what US researchers investigated in a nested case controlled study, recently published in JAMA. The study was based on a cohort of adult women from the Kaiser Permanente Washington health care system who had had a pelvic ultrasound at some stage over a 12-year period starting in 1997, and looked at the association of the ultrasound finding with the risk of being diagnosed with ovarian cancer within three years. On analysing the data from the 72,000 women who underwent the investigation, the first finding was that ovarian cysts were very common, particularly simple ovarian cysts, occurring in more than 15,000 women. Simple cysts were detected in almost one in four women aged younger than 50, and just over one in 12 women aged 50 and over. Complex cyst structures were far less common, which is fortunate as the study also confirmed that most of the 212 women who were eventually diagnosed with ovarian cancer had a complex cyst structure on ultrasound. According to their analysis, the detection of a complex cystic ovarian mass on ultrasound increased the likelihood of cancer eight-fold, and if they were 50 or over and found to have ascites as well, the finding was practically diagnostic with the likelihood of having ovarian cancer being over 70 times greater than normal. Ultrasound detection of solid masses was not as dangerous a finding, but the one in ten association with ovarian cancer certainly warranted further investigation. But what of the women found to have a simple cyst on ultrasound? How many of them went on to be diagnosed with ovarian cancer? Well, among those aged under 50 – none! And among the older women only one – and the researchers suspect that the simple cyst found in this case was, in fact an incidental finding. As the study authors point out, this finding shouldn’t be surprising as it is well-known that ‘simple cysts are almost universally benign.’ But the majority of guidelines still recommend on-going surveillance, mainly because of a reluctance to make a definitive diagnosis on the basis of the ultrasound appearance or interpretation alone. “One of the justifications for the surveillance of simple cysts is that imaging may be inaccurate and might miss complex features,” the researchers explain. But such concerns are not warranted according to this study. What’s more, the authors suggest the constant monitoring of these benign cysts may in fact not only be useless but may cause harm. “While surveillance may not seem harmful, there is a growing realisation across all areas of medicine that unnecessary imaging is associated with morbidity, including wasted time, false-positive results, over diagnosis, unnecessary surgery and anxiety,” the study authors concluded.  

Reference

Smith-Bindman R, Poder L, Johnson E, Miglioretti DL. Risk of Malignant Ovarian Cancer Based on Ultrasonography Findings in a Large Unselected Population. JAMA Intern Med. Published online November 12, 2018. doi:10.1001/jamainternmed.2018.5113.
Dr Linda Calabresi

Australian research has found an increased risk of intellectual disability with some forms of Assisted Reproductive Technology (ART). The WA study published in Pediatrics found that one in 48 children conceived using ART were diagnosed with an intellectual disability, compared with only one in 59 children conceived naturally. And the risk was even greater for certain subgroups within the ART cohort. “The risk was more than doubled for those born very preterm, for severe [intellectual disability] and after intracytoplasmic sperm injection (ICSI) treatments,” said the researchers from the Telethon Kids Institute. To conduct the study, researchers analysed population registers of over 200,000 live births occurring between 1994 and 2002 in Western Australia and examined data on ART and diagnoses of intellectual disability occurring within eight years of follow-up. The fact that the study findings were based on analyses of statistics from almost 20 years ago was acknowledged by the authors, especially since ART practices have changed greatly since then. “Our study included children born from 1994 to 2002 when multiple embryo transfer was common practice in Western Australia,” they said. This increased the likelihood of a multiple pregnancy and preterm birth. However even when the analyses are restricted to singleton births the small increased risk of intellectual disability persisted but was not as great. The link between ICSI-conceived children and intellectual disability was also of interest. At the time, this technique was restricted to couples with severe male-factor subfertility and was often associated with older aged males. “Genetic abnormalities occur more frequently in men who are infertile, so ICSI (which bypasses natural selection barriers) may allow for the transmission of chromosomal anomalies in the offspring,” the authors said. According to the study, one in 32 children conceived using ICSI were diagnosed with an intellectual disability. ICSI is now used more broadly, prompting concerns. As lead author, Dr Michele Hansen said, “[ICSI] is currently used in 63 per cent of treatment cycles.” “Our findings show an urgent need for more recent data to establish whether the increased risks of intellectual disability seen in children conceived using ICSI are solely related to severe male subfertility and older paternal age, or if there are other risks associated with the technique itself.” Overall the study findings provide supportive evidence for Australia’s current IVF policy of single embryo transfer unlike many other countries where multiple embryo transfers are still routinely performed. The researchers also point out the study has implications for the use of ICSI, or more exactly restricting the use of ICSI and recognising the increased risk of genetic anomalies that might occur in children conceived in this way. “These couples may opt to use preimplantation genetic testing to maximise the transfer of chromosomally normal embryos,” they suggest.  

Reference

Hansen M, Greenop KR, Bourke J, Baynam G, Hart RJ, Leonard H. Intellectual Disability in Children Conceived Using Assisted Reproductive Technology. Pediatrics. 2018; 142(6): e20181269. DOI 10.1542/peds.2018-1269
Dr Linda Calabresi

Women with a normal BMI can no longer tick off weight as breast cancer risk factor, US researchers say. According to their study, published in JAMA Oncology, it’s body fat that increases the risk even if the woman falls into a healthy weight range. The study was in fact a secondary analysis of the Women’s Health Initiative clinical trial along with observational study cohorts involving almost 3500 post-menopausal, healthy BMI women who at baseline had their body fat analysed (by DXA) and were then followed up for a median duration of 16 years. What the researchers discovered was that women in the highest quartile for total body fat and trunk fat mass were about twice as likely to develop ER-positive breast cancer. “In this long-term prospective study of postmenopausal with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancers,” the study authors spelled. Perhaps less surprisingly, the analysis also found that the breast cancer risk increased incrementally as the body fat levels increased. “We found a 56% increase in the risk of developing ER-positive breast cancer per 5-kg increase in trunk fat, despite a normal BMI,” they said. The proposed mechanism that explains why high body fat levels increases the risk of breast cancer, is much the same as the known mechanism that explains the link between obesity and breast cancer risk. People with high body fat levels tend to have adipocyte hypertrophy and cell death which means the adipose tissue is chronically although sub-clinically inflamed. This inflammation triggers the production of a number of factors including an increased ratio of oestrogens to androgens which is believed to predispose to the development of oestrogen-dependent breast cancer. Basically the study authors believe these women with high body fat but normal BMI, are ‘metabolically obese’ even though they do not fit the standard definition of obese. And while using DXA to determine body fat levels is highly accurate, such an assessment is rarely used in everyday practice. Most doctors look only at BMI measurements or they may also assess waist measurement which has variable sensitivity in terms of diagnosing excess body fat. Consequently, the researchers say, many non-overweight women who are at increased risk of breast cancer because of their high adiposity may be going unrecognised. So where does that leave us? Here the study authors were less definitive. The link between body fat and breast cancer is clear but, they say, more research is needed to determine the most appropriate management for this cohort of women with high body fat levels and normal BMI. “Future studies are needed to determine whether interventions that reduce fat mass, such as diet and exercise programs or medications including aromatase inhibitors, might lower the elevated risk of breast cancer in this population with normal BMI,” they concluded.

Reference

Iyengar NM, Arthur R, Manson JE, Chlebowski RT, Kroenke CH, Peterson L, et al. Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index: A Secondary Analysis of a Randomized Clinical Trial and Observational StudyJAMA 2018 Dec 6. DOI: [10.1001/jamaoncol.2018.5327] [Epub ahead of print]
Martyn Lloyd Jones

For many years experts in the field of drug policy in Australia have known existing policies are failing. Crude messages (calls for total abstinence: “just say no to drugs”) and even cruder enforcement strategies (harsher penalties, criminalisation of drug users) have had no impact on the use of drugs or the extent of their harmful effects on the community. Whether we like it or not, drug use is common in our society, especially among young people. In 2016 43% of people aged 14 and older reported they had used an illicit drug at some point in their lifetime. And 28% of people in their twenties said they had used illicit drugs in the past year. The use of MDMA (the active ingredient in ecstasy) is common and increasing among young people. In the last three months alone five people have died as a result of using illicit drugs at music festivals and many more have been taken to hospital. The rigid and inflexible attitudes of current policy-makers contrast dramatically with the innovative approaches to public health policy for which Australia was once renowned. Since the 1970s many highly successful campaigns have improved road safety, increased immunisation rates in children and helped prevent the spread of blood-borne virus infections. The wearing of seatbelts was made compulsory throughout Australia in the early 1970s. Randomised breath testing and the wearing of helmets by bike riders were introduced in the 1980s. These measures alone have saved many thousands of lives. The introduction of needle exchange and methadone treatment programs in the late 1980s and, more recently, widespread access to effective treatments for hepatitis C have dramatically reduced the health burden from devastating infections such as HIV and the incidence of serious liver disease. Each of these programs had to overcome vigorous and sustained hostility from opponents who argued they would do more harm than good. But in all cases the pessimists were proved wrong. Safety measures on the roads did not cause car drivers and bike riders to behave more recklessly. The availability of clean needles did not increase intravenous drug use. Easier access to condoms did not lead to greater risk taking and more cases of AIDS. We believe — along with many other experts in the field — that as was the case for these earlier programs, the evidence presently available is sufficient to justify the careful introduction of trials of pill testing around Australia. Specifically, we support the availability of facilities to allow young people at venues or events where drug taking is acknowledged to be likely to seek advice about the substances they’re considering ingesting. These facilities should include tests for the presence of known toxins or contaminants to help avert the dangerous effects they may produce. Such a program should be undertaken in addition to, and not instead of, other strategies to discourage or deter young people from taking illicit drugs. Although pill testing has been widely and successfully applied in many European countries over a twenty year period, it has to be admitted the evidence about the degree of its effectiveness remains incomplete. That’s why any program in Australia should be linked to a rigorously designed data collection process to assess its impact and consequences. However, we do know that the argument that pill testing programs will increase drug use and its associated harms is very unlikely to be true. Most people seeking advice about the constituents of their drugs will not take them if they are advised that they contain dangerous contaminants. And it’s easy to avoid false reassurances about safety by careful explanations and detailed information. The opportunity to provide face-to-face advice to young people about the risks of drug taking is one of the great strengths of pill testing programs. Over the last half century we have learnt public health programs have to utilise multiple strategies and provide messages carefully and tailored for different audiences. What works to combat the harms associated with drug-taking in prisons is different from what works for specific cultural groups or for young people attending music festivals. The available evidence suggests pill testing is an effective and useful approach to harm minimisation in this last group. We believe it has the capacity to decrease ambulance calls to festival-goers, help change behaviour and save lives. It has taken until now for pill testing techniques to be developed to a level where they are able to identify the constituents in analysed samples with sufficient precision, reliability and speed. These techniques, and the range of substances for which they can test, will continue to improve over time. On the basis of experience gained in the UK, Europe and Australia it’s clear pill testing is now feasible and practicable. The members of the Australasian Chapter of Addiction Medicine within the Royal Australasian College of Physicians are the main clinical experts in the field of addiction medicine in this country. Together with the Australian Medical Association and many prominent members of the community with experience in this area we feel this is the time for pill testing to be introduced, albeit in careful and controlled circumstances. We believe this position is also supported by peer users, concerned families, and past and present members of police forces across Australia. The fact the “War on Drugs” has failed does not mean we should give up. There are many new weapons available to us, as we have learnt from the successful public health campaigns of the past. Pill testing will not abolish all the harms associated with drug taking, but if handled carefully, carries the likelihood of reducing them significantly. Martyn Lloyd Jones, Honorary Senior Lecturer, University of Melbourne and Paul Komesaroff, Professor of Medicine, Monash University This article is republished from The Conversation under a Creative Commons license. Read the original article.

Dr Linda Calabresi

While it appears the message about risky drinking is getting through to younger Australians, baby boomers are as bad as ever. According to a research letter appearing in the latest edition of the MJA, the proportion of 55-70-year-olds who could be classed as high-risk drinkers has risen over the last 15 or so years. The South Australian researchers say this is in ‘stark contrast to the significant decrease in risky drinking among people aged between 12-24 years during the same period.’ And while they do emphasise that by far the majority of older Australians (over 80%) are abstainers or drink at low risk levels, the proportional increase of those now in the high-risk category (from 2.1% in 2004 to 3.1% in 2016) represents an additional 400,000 at-risk individuals – significant in anyone’s language. The findings were based on secondary analyses of data from National drug Strategy Household Surveys conducted in 2004, 2007, 2010, 2013 and 2016. Interestingly the researchers defined the risk categories on the basis of the maximum number of standard alcoholic drinks drunk on a single occasion over the course of a month. So low-risk were those individuals who never consumed more than four drinks in a single session, risky drinkers drank 5-10 drinks in one session at least once a month and high-risk drinkers needed to have drunk 11 or more drinks at least once a month. It’s a slightly different means of assessment to the more common approach of asking about average daily alcohol intake and appears more likely to detect the binge drinker – or your classic ‘social drinker.’ As the letter authors point out, detecting problem drinking in this age group is especially important as this cohort is particularly vulnerable to a range of alcohol-related adverse events from falls to diabetes. Once again, the researchers are looking to GPs to detect those at-risk from drinking among our baby boomer patient population and initiate evidence-based interventions, such as short, opportunistic counselling and information sessions. But they recognise this isn’t always easy. “To facilitate early identification of problem drinking and early intervention, educating health care professionals about patterns and drivers of alcohol consumption by older people should be a priority,” the authors said. Perhaps using the study’s categorisation technique of the maximum number of drinks consumed in a single session might go some way to detecting those at risk.  

Referernce:

Roche AM, Kostadinov V. Baby boomers and booze: we should be worried about how older Australians are drinking. Med J Aust. 2019; 210(1): 38-9. DOI: 10.5694/mja2.12025. Available from: https://www.mja.com.au/journal/2019/210/1/baby-boomers-and-booze-we-should-be-worried-about-how-older-australians-are
Dr Linda Calabresi

At first read, the study results seemed disappointing. Yet another promising premise fails to deliver when it comes to actual proof. But the researchers aren’t ready to give up on this hypothesis just yet. In fact, commentators on the study say the results offer ‘great hope’ and represent ‘a major leap forward.’ The SPRINT MIND study, recently published in JAMA was investigating whether intensive blood pressure control (to a systolic less than 120mmHg) worked better than standard blood pressure control (SBP<140mmHg) at reducing the risk of mild cognitive impairment and dementia. This randomised controlled trial was a component of the well-publicised Systolic Blood Pressure Intervention Trial (SPRINT) which looked at the effect of more intensive blood pressure control on cardiovascular and renal outcomes in addition to cognitive function in over 9000 people without a history of diabetes or stroke. Basically, what this study showed was that intensive blood pressure control to a target of less than 120mmHg did not reduce the incidence of probable dementia compared to lowering BP to a target of less than 140mmHg. Depressing, yes? No, say the study authors. Firstly, they say the study demonstrated no ill-effects of intensive BP lowering – which has been an issue of concern for some who have been worried that lowering the BP could decrease cerebral perfusion thereby harming cognitive function. In fact, the study authors showed quite the opposite was true. The intervention actually helped protect cognitive ability. “This is the first trial, to our knowledge, to demonstrate an intervention that significantly reduces the occurrence of [mild cognitive impairment], a well-established risk factor for dementia, as well as the combined occurrence of [mild cognitive impairment] or dementia,” they said. The study authors suggest the lack of benefit in dementia may be due to the fact the SPRINT study was terminated early following the demonstration of benefit of intensive BP control on cardiovascular outcomes and all-cause mortality. Because of this shortened time frame and the fact that there were fewer than expected cases of dementia, they suggest the study may have been ‘underpowered’ to show a result for lowering the risk of dementia. They also say there were fewer cases of dementia among the intensive treatment group compared with the standard treatment group (7.2 vs 8.6 cases per 1000 patient years) even though this wasn’t statistically significant. We cannot know whether this trend would have reached statistical significance had the intervention continued. An accompanying editorial views the study and the results with a good deal of positivity. “For older adults, almost all of who have concern about being diagnosed with Alzheimer Disease and related dementia, [this study] offers great hope,” the US epidemiologist, Dr Kristine Yaffe, said. She points out that this a readily modifiable risk factor, and we should be accelerating our efforts into investigating whether this, along with other vascular health interventions such as physical activity, can indeed prevent dementia, building on the positive results of this study. “The SPRINT MIND study may not be the final approach for prevention of Alzheimer disease or other cognitive impairment but it represents a major leap forward in what has emerged as a marathon journey.”

Reference

Yaffe, K. Prevention of Cognitive Impairment With Intensive Systolic Blood Pressure Control. JAMA [Internet]. 2019 Jan 28. DOI: 10.1001/jama.2019.0008 [Epub ahead of print]